Determinants of aspirin resistance in patients with type 2 diabetes

BackgroundCardiovascular disease is a leading cause of mortality among patients with type 2 diabetes mellitus (T2DM). Numerous patients with T2DM show resistance to aspirin treatment, which may explain the higher rate of major adverse cardiovascular events observed compared with non-diabetes patients, and it has recently been shown that aspirin resistance is mainly related to accelerated platelet turnover with persistent high platelet reactivity (HPR) 24 h after last aspirin intake. The mechanism behind HPR is unknown. The aim of this study was to investigate the precise rate and mechanisms associated with HPR in a population of T2DM patients treated with aspirin.MethodsIncluded were 116 consecutive stable T2DM patients who had attended our hospital for their yearly check-up. HPR was assessed 24 h after aspirin intake using light transmission aggregometry (LTA) with arachidonic acid (AA) and serum thromboxane B2 (TXB2) measurement. Its relationship with diabetes status, insulin resistance, inflammatory markers and coronary artery disease (CAD) severity, using calcium scores, were investigated.ResultsUsing LTA, HPR was found in 27 (23%) patients. There was no significant difference in mean age, gender ratio or cardiovascular risk factors in patients with or without HPR. HPR was significantly related to duration of diabetes and higher fasting glucose levels (but not consistently with HbA_1c), and strongly related to all markers of insulin resistance, especially waist circumference, HOMA-IR, QUICKI and leptin. There was no association between HPR and thrombopoietin or inflammatory markers (IL-6, IL-10, indoleamine 2,3-dioxygenase activity, TNF-α, C-reactive protein), whereas HPR was associated with more severe CAD. Similar results were found with TXB2.ConclusionOur results reveal that ‘aspirin resistance’ is frequently found in T2DM, and is strongly related to insulin resistance and severity of CAD, but weakly related to HbA_1c and not at all to inflammatory parameters. This may help to identify those T2DM patients who might benefit from alternative antiplatelet treatments such as twice-daily aspirin and thienopyridines.     

Prevalence of aspirin resistance in patients with type 2 diabetes

Abstract Aspirin resistance has been recognised to occur in patients with cardiovascular disease and is associated with poor clinical prognosis. The purpose of the present study was to evaluate the prevalence of aspirin resistance in 172 patients with diabetes mellitus type 2 (DM-2). Platelet function of 172 consecutive patients with type 2 diabetes on chronic aspirin therapy was evaluated. The effect of aspirin was assessed using the platelet function analyser (PFA-100) system, reporting platelet-dependent thrombus formation as the time required to close a small aperture in a biologically active membrane. Resistance to aspirin was defined as a normal collagen/epinephrine-induced closure time (82–165 s). Aspirin responders were defined when closure time was 300 s. Thirty-seven (21.5%) of the type 2 diabetic patients were found to be resistant to chronic aspirin therapy, 29 (16.9%) were semi-responders and 106 (61.6%) were responders. Univariate analysis revealed that aspirin non-responders were significantly younger (p<0.05) compared to aspirin responders. A significant number of type 2 diabetic patients are resistant to aspirin therapy. Aspirin resistance can be evaluated by point-of-care testing and should be recognised in diabetic patients that are treated for primary or secondary prevention.     

Non-HDL cholesterol is a better target for predicting periprocedural myocardial injury following percutaneous coronary intervention in type 2 diabetes

Objective: Non-HDL cholesterol (non-HDL-C) has recently been recommended as a first target for dyslipidemia management. We previously reported that LDL cholesterol (LDL-C) and non-HDL-C levels were similarly associated with periprocedural myocardial injury (PMI) following percutaneous coronary intervention (PCI) in patients with coronary artery disease. Here we investigated the comparative prognostic value of non-HDL-C and LDL-C for PMI following PCI in type 2 diabetes (T2D). Methods: We prospectively enrolled 1194 consecutive T2D patients with normal preprocedural cTnI undergoing PCI. Patients were divided into the two groups: group A [glycated hemoglobin (HbA1c) < 7%, n = 567] and group B (HbA1c ≥ 7%, n = 627). PMI was evaluated by cTnI analysis within 24 h. The relationship of preprocedural non-HDL-C and LDL-C levels with peak cTnI values after PCI was examined. Results: Patients in group B, with higher preprocedural non-HDL-C levels, had higher postprocedural cTnI levels (β = 0.102, P = 0.011). In the multivariable model, a 1-SD increase in non-HDL-C produced a 30% and 33% increased risk of postprocedural cTnI >3 × upper limit of normal (ULN) and >5 × ULN in group B, respectively. However, neither LDL-C nor group A patients were affected. Furthermore, patients with non-HDL-C levels ≥130 mg/dl compared with non-HDL-C levels ≤100 mg/dl were associated with a 83.3% and 71.7% increased risk of postprocedural cTnI >3 × ULN and >5 × ULN in group B, respectively. Conclusions: In poorly-controlled diabetic patients (HbA1c ≥ 7%) undergoing PCI, non-HDL-C but not LDL-C was independently associated with and increased risk of PMI, and non-HDL-C levels ≥130 mg/dl had a worse PMI risk profile compared with non-HDL-C levels <100 mg/dl.     

老年2型糖尿病患者阿司匹林抵抗的发生率及相关危险因素分析

目的 评价老年2型糖尿病患者阿司匹林抵抗的发生率及可能的危险因素.方法 140例老年2型糖尿病患者,年龄60～92岁,平均(73.8±8.0)岁,口服阿司匹林(≥75 mg)1个月以上.血小板聚集功能采用血小板聚集试验(LTA)和血栓弹力图法(TEG)评价.结果 LTA法检测6例(4.3%)患者为阿司匹林抵抗,44例(31.4%)患者为阿司匹林半抵抗.TEG法检测31例(22.1%)患者为阿司匹林抵抗,其中LTA法显示3例.经TEG法检测分组多因素回归分析结果显示,女性(OR=5.54,95%CI:1.17～27.47,P=0.036)、同型半胱氨酸水平(OR=1.15,95%CI:1.00～1.35,P=0.043)为阿司匹林抵抗的危险因素.结论 老年2型糖尿病患者阿司匹林抵抗发生率较高,阿司匹林抵抗更易发生在女性、高同型半胱氨酸水平的患者.     

2型糖尿病对阿司匹林和氯吡格雷双联抗血小板药物治疗效应的分析

目的:本研究通过前瞻性连续入选在我院因稳定性冠心病行经皮冠状动脉介入治疗(PCI)的患者,分析探讨糖尿病对阿司匹林和氯吡格雷双联抗血小板药物效应的影响。方法:2008年8月至2011年11月前瞻性连续入选稳定性冠心病患者。入院后服用氯吡格雷前测定花生四烯酸(AA)诱导的血小板聚集率和基线二磷酸腺苷(ADP)诱导的血小板聚集率,之后给予氯吡格雷300 mg负荷量口服,继续服用氯吡格雷75 mg/d至1 d后,再次测定服用氯吡格雷后ADP诱导的血小板聚集率。结果:入选了355例稳定性冠心病患者,其中合并2型糖尿病103例,非糖尿病252例。阿司匹林抵抗的发生率18.6%,糖尿病组与非糖尿病组阿司匹林抵抗的发生率未见明显差异(20.4%vs.17.9%,P=0.578),将患者基线特征纳入Logistic回归模型进行校正后结果显示,糖尿病并未增高阿司匹林抵抗的风险(OR=1.3,95%CI=0.7～2.7,P=0.439)。氯吡格雷抵抗的发生率为20.8%;糖尿病组氯吡格雷抵抗的发生率明显高于非糖尿病组(33.0%vs.15.9%,P<0.001);Logistic回归校正后结果显示,糖尿病是氯吡格雷抵抗的独立危险因素(OR=5.7,95%CI=2.9～11.1,P<0.001)。结论:双联抗血小板药物基础上,糖尿病未增高阿司匹林抵抗的风险;但是糖尿病明显增高了氯吡格雷抵抗的风险。     

老年2型糖尿病合并冠心病患者阿司匹林抵抗的危险因素分析

目的 研究老年T2DM合并冠心病患者对阿司匹林的反应性及其危险因素. 方法 选择我院老年科住院的T2DM合并冠心病患者147例,根据血栓弹力图（TEG）结果将其分为阿司匹林抵抗组（AR,抑制率≤50％）和阿司匹林非抵抗组（N-AR）,并分析两组临床数据. 结果 AR组30例,N-AR组117例.AR发生率为20％.AR组同型半胱氨酸（Hcy）、FPG、TG、LDL-C及HbA1c分别为（16.43±4.77）mmol/L,（7.73±0.16）mmol/L,（1.70±0.60） mmol/L,（2.60±0.55） mmol/L,（7.79±0.58）％,均明显高于N-AR组,而视黄醇结合蛋白（RBP）为（34.17±9.30） mmol/L,低于NAR组（P＜0.05）.Logistic回归分析结果显示,FPG、TC、LDL-C和Hcy是AR的影响因素,使患者AR的危险性分别提高1.9倍,0.1倍,13.1倍和1.1倍.血糖不达标者、糖尿病病程较长者AR发生率增高（P＜0.05）.结论 T2DM合并冠心病患者存在一定的AR现象,有效地控制血糖,减低血脂,降低Hcy,可降低AR发生率.     

Utility of non-high-density lipoprotein cholesterol in assessing incident type 2 diabetes risk

Aims: Traditional lipid indices have been associated with type 2 diabetes, but limited data are available regarding non‐high‐density lipoprotein (non‐HDL) cholesterol. In view of recent guidelines for the clinical management of dyslipidemia recommending the monitoring of non‐HDL cholesterol as a secondary target after achieving the low‐density lipoprotein (LDL) cholesterol goal, we aimed to assess the association of non‐HDL cholesterol with incident type 2 diabetes and compare its utility as a risk predictor with traditional lipid variables in Aboriginal Canadians. Methods: Of 606 diabetes‐free participants at baseline, 540 (89.1%) returned for 10‐year follow‐up assessments. Baseline anthropometry, blood pressure, fasting insulin and serum lipids were measured. Fasting and 2‐h postload glucose were obtained at baseline and follow‐up to determine the incidence of type 2 diabetes. Results: The cumulative incidence of type 2 diabetes was 17.5%. Higher non‐HDL cholesterol, total‐to‐HDL cholesterol ratio, apolipoprotein B, triglyceride and LDL cholesterol and lower HDL cholesterol concentrations were individually associated with incident type 2 diabetes in univariate analyses (all p < 0.05). Non‐HDL cholesterol was a superior determinant of incident diabetes compared with LDL cholesterol (comparing C‐statistics of univariate models p = 0.01) or HDL cholesterol (p = 0.004). With multivariate adjustment including waist circumference, non‐HDL cholesterol remained associated with incident diabetes [odds ratio (OR) 1.42 (95% confidence interval, CI 1.07–1.88)], while LDL cholesterol and HDL cholesterol became non‐significant. Conclusions: Non‐HDL cholesterol was associated with incident type 2 diabetes and was superior to LDL cholesterol as a risk predictor in this population. Further studies are required to establish the utility of non‐HDL cholesterol in non‐Aboriginal populations.     

2型糖尿病家族史是糖耐量正常个体发生代谢综合征的独立危险因素

目的研究糖耐量正常（NGT）的2型糖尿病（T2DM）一级亲属中代谢综合征（MS）的相关危险因素。方法采用横断面研究，比较182例T2DM家族史阳性（FH^＋）与126例家族史阴性（FH^-）NGT个体的人体测量指标和代谢参数的差异，分析MS的相关危险因素。结果FH^＋个体的腰围和OGTT血糖曲线下面积显著高于FH^-个体，而胰岛β细胞功能指数则显著低于FH^-个体。Logistic分析显示，T2DM家族史是MS和中心性肥胖的独立危险因素，OR值分别为3．33和2．59；中心性肥胖是高血压、高TG血症及低HDL-C血症的独立危险因素，OR值分别为1．41、1．43及1、07。结论T2DM家族史可能是NGT的一级亲属发生中心性肥胖和MS的独立危险因素。早期生活方式干预可使该人群避免发生中心性肥胖，从而减少发生MS甚或心血管疾病的风险。     

Prevalence of and risk factors for aspirin resistance in elderly patients with coronary artery disease

Objective To assess the prevalence of and related risk factors for aspirin resistance in elderly patients with coronary artery disease (CAD). Methods Two hundred and forty-six elderly patients (75.9 ± 7.4 years) with CAD who received daily aspirin therapy (≥ 75 mg) over one month were recruited. The effect of aspirin was assessed using light transmission aggregometry (LTA) and thrombelastography platelet mapping assay (TEG). Aspirin resistance was defined as ≥ 20% arachidonic acid (AA)-induced aggregation and ≥ 70% adenosine diphosphate (ADP)-induced aggregation in the LTA assay. An aspirin semi-responder was defined as meeting one (but not both) of the criteria described above. Based on the results of TEG, aspirin resistance was defined as ≥ 50% aggregation induced by AA. Results As determined by LTA, 23 (9.3%) of the elderly CAD patients were resistant to aspirin therapy; 91 (37.0%) were semi-responders. As determined by TEG, 61 patients (24.8%) were aspirin resistant. Of the 61 patients who were aspirin resistant by TEG, 19 were aspirin resistant according to LTA results. Twenty-four of 91 semi-responders by LTA were aspirin resistant by TEG. Multivariate logistic regression analysis revealed that elevated fasting serum glucose level (Odds ratio: 1.517; 95% CI: 1.176–1.957; P = 0.001) was a significant risk factor for aspirin resistance as determined by TEG. Conclusions A significant number of elderly patients with CAD are resistant to aspirin therapy. Fasting blood glucose level is closely associated with aspirin resistance in elderly CAD patients.     

Glycemic profile variability: An independent risk factor for diabetic neuropathy in patients with type 2 diabetes

BackgroundImpaired glycemic control is a potential predictor for macro- and microvascular complications of diabetes, which could be recognized by glycemic variability. The aim of this 10-year prospective cohort study presented here is to gain a better understanding of the correlation between GV and diabetic peripheral neuropathy (DPN) as one of the most common complications of T2DM.MethodsSince February 2010, 1152 adult patients with T2DM have been followed-up. Baseline features, anthropometric measurements, and laboratory findings were collected and documented during ten years. The association between DPN incidence and glycemic profile variability was evaluated using cox regression analysis. The coefficient of variation of glycemic indices within subjects was calculated and compared using an independent sample t-test.ResultsIndividuals who developed neuropathy had significantly higher mean levels of glycemic indices (HbA1c, FBS, and 2hpp), urinary albumin excretion, mean creatinine levels, and a longer duration of diabetes. A significant positive correlation between incidence of DPN and glycemic profile variability (cv-FBS10 %, cv-FBS20 %, cv-2hpp20 %, cv-HbA1c5 % and cv-HbA1c10 %) was revealed. Results also showed that higher variability of FBS was associated with the higher risk of neuropathy incidence (HR: 12.29, p-value: 0.045), which indicates that glycemic profile variability is an independent risk factor for DPN in patients with T2DM.ConclusionVariability of glycemic profiles from a visit to visit, regardless of sustained hyperglycemia, was indeed a significant risk factor for DPN in diabetic type 2 patients. CV-FBS was the most critical glycemic variability indices for DPN development.     

代谢综合征患者阿司匹林抵抗的临床研究

目的探讨代谢综合征患者阿司匹林抵抗的发生率和临床特征。方法对2005年5月至6月北京首钢社区人群中221例病情稳定的代谢综合征患者,口服阿司匹林200mg/d共10d后,应用血小板聚集仪测定花生四烯酸(AA)诱导的血小板聚集率。以0.5g/LAA诱导的血小板平均聚集率≥20%为阿司匹林抵抗。结果阿司匹林抵抗发生率为17.6%(39/221)。阿司匹林抵抗(AS)组患者的纤维蛋白原水平显著高于阿司匹林敏感(AR)组的患者[(2.6±0.4)g/L对(2.4±0.4)g/L,P=0.017)]。两组患者的血压、年龄、空腹血糖、血脂以及体重指数等差异均无统计学意义;性别、吸烟、既往心梗或脑梗病史的分布也无统计学意义。进一步根据患者性别进行分层分析发现,在男性患者中心梗病史是阿司匹林抵抗的预测因素(50%对14.5%,P=0.020),在女性患者中舒张压高于85mmHg(1mmHg=0.133kPa)是阿司匹林抵抗的预测因素(34.0%对15.5%,P=0.043)。结论研究人群中阿司匹林抵抗的发生率为17.6%,高纤维蛋白原是阿司匹林抵抗的危险因素,心梗病史和较高的舒张压可能分别是男性和女性阿司匹林抵抗的预测因素。     

Age ≥ 60 years was an independent risk factor for diabetes-related complications despite good control of cardiovascular risk factors in patients with type 2 diabetes mellitus

Providing effective medical care for older patients with type 2 diabetes mellitus (T2D) that may contribute to their active aging has always been challenging. We examined the independent effect of age ≥ 60 years on disease control and its relationship with diabetes-related complications in patients with T2D in Malaysia. This was a cross-sectional study using secondary data from the electronic diabetes registry database Adult Diabetes Control and Management (ADCM). A total of 303 centers participated and contributed a total of 70,889 patients from May 2008 to the end of 2009. Demographic data, details on diabetes, hypertension, dyslipidemia and their treatment modalities, various risk factors and complications were updated annually. Independent associated risk factors were identified using multivariate regression analyses. Fifty-nine percent were female. Malay comprised 61.9%, Chinese 19% and Indian 18%. There were more Chinese, men, longer duration of diabetes and subjects that were leaner or had lower BMI in the older age group. Patients aged ≥ 60 years achieved glycemic and lipid targets but not the desired blood pressure. After adjusting for duration of diabetes, gender, ethnicity, body mass index, disease control and treatment, a significantly higher proportion of patients ≥ 60 years suffered from reported diabetes-related complications. Age ≥ 60 years was an independent risk factor for diabetes-related complications despite good control of cardiovascular risk factors. Our findings caution against the currently recommended control of targets in older T2D patients with more longstanding diseases and complications.     

心血管病患者中的阿司匹林抵抗

目的　前瞻性地评价心血管病患者发生阿司匹林抵抗 (AR)的流行病学概况 ,并探讨其预测因子。方法　 35 2例病情稳定的心血管病住院患者 ,每日服用阿司匹林 10 0mg ,连服 7天 ,服用最后一剂后 2 4h内抽取的空腹静脉血为血样 ,分别用二磷酸腺苷 (ADP)、花生四烯酸 (AA)诱导血小板凝集试验 (PAgT) ,检测血小板聚集率。结果　患者中AR发生率为 3.98% ,阿司匹林半敏感 (ASR)者占 2 5 .9% ,且AR或ASR患者中的女性较AS者多(35 .2 %vs 18.2 % ,P =0 .0 0 1) ,而AS者中吸烟者较AR或ASR者多 (0 %vs 9.5 % ,P =0 .0 0 2 )。结论　阿司匹林用于抗血小板治疗及预防动脉硬化事件的心血管病患者 ,若有AR存在可选择其他安全有效的抗血小板制剂长期服用 ,预测AR及抗血小板治疗个体化 ,将是抗血小板治疗未来的方向     

Non-HDL cholesterol level is reliable to be an early predictor for vascular inflammation in type 2 diabetes mellitus

Although LDL is the primary target for lipid-lowering therapy and non-HDL cholesterol is a secondary target in patients with elevated triglyceride (TG) levels, non-HDL cholesterol is still an early, reliable, and practical predictor for vascular inflammation. However, in comparison with LDL, further evidence for superiority in non-HDL cholesterol as the primary therapeutic target is required. A total of 189 type 2 diabetic patients (88 men and 101 women; mean age 58.4 +/- 14.0 years; duration of diabetes 9.8 +/- 4.2 years) who had not used anti-inflammatory agents in the past two years were enrolled in this study. Levels of various lipid fractions and C-reactive protein (CRP) and the cholesterol retention fraction (CRF) were measured. Lipid levels and CRF in samples with CRP levels below or above different cutoffs were compared. Statistically significant differences were seen at all CRP cutoffs in the levels of TG, HDL, and non-HDL cholesterol and the CRF, but no differences were seen in total cholesterol and LDL cholesterol levels. CRP levels correlated with non-HDL cholesterol levels (r = 0.16, P = 0.0236) and the CRF (r = 0.18, P = 0.14), but not with levels of HDL or TG. Besides, non-HDL levels showed a marked correlation with CRF (r = 0.68, P < 0.0001). On the basis of CRP levels, non-HDL levels are reliable in predicting vascular inflammation, and CRF could be another important predictor for cardiovascular events. Our results suggest that the emphasis placed on non-HDL cholesterol should be reevaluated in comparison with that placed on LDL cholesterol.     

Insulin resistance and NAFLD may influence memory performance in obese patients with prediabetes or newly-diagnosed type 2 diabetes

Background and aimsDiabetes has consistently been shown to increase risk for cognitive decline. Cognitive deficits may occur at the very earliest stages of diabetes.We sought to estimate the determinants of memory function in a group of middle-aged obese subjects with prediabetes or newly-diagnosed type 2 diabetes mellitus.Methods and resultsSixty-two obese patients in treatment with metformin-with prediabetes (n = 41) or newly diagnosed T2DM (n = 21), were studied. Short- and long-term memory function was assessed through a neuropsychological assessment consisting of two tests and a composite domain z score was calculated. Cardiometabolic variables, such as abdominal MRI quantification of subcutaneous (SAT) and visceral (VAT) adipose tissue content, and of intra-hepatocellular lipid content, as well as insulin sensitivity (Matsuda Index, HOMA-IR) and beta cell performance (Beta Index), by multiple sampling, 8-point oral glucose tolerance test, were also evaluated.Age, non-alcoholic fatty liver disease (NAFLD), and lnHOMA-IR together explained 18% (R square) of the variance in memory domain. Including NAFLD increased the explained variance by 8% and including lnHOMA-IR by 9.1%, whereas the contribution of age and other factors was negligible.ConclusionPreventing and managing insulin resistance in precocious and possibly earlier stages of diabetes might provide benefit in slowering down future cognitive decline.     

2型糖尿病患者合并脂肪肝的多因素分析

目的 探讨影响糖尿病合并脂肪肝的主要危险因素。方法 294例住院治疗的糖尿病患者根据B超检查结果分为糖尿病合并脂肪肝的主要危险因素。方法 294例住院治疗的糖尿病患者根据B超检查结果分为糖尿病合并脂肪肝组（DFL）与糖尿病对照组（DM组），并收集同期的非糖尿病非酒精性脂肪肝（NASH）患者49例作为对照。结果 （1）糖尿病合并脂肪肝的发病率为41.15%;(2)与DFL有关的危险因素包括体重，体重指数，腰臂比值，血压，空腹胰岛素，餐后2小时胰岛素，胆固醇，甘油三酯，载脂蛋白B，HOMA-IR，其中最主要的两个危险因素是甘油三酯和体重指数；（3）糖尿病患者的性别，年龄，糖尿病病程，血糖和血清转氨酶水平两组比较，差异无显著性；（4）DFL与非糖尿病NASH比较，HOMA-IR差异无显著性。结论 （1）影响DFL的因素众多，主要因素是甘油三酯和体重指数；（2）虽然性别，血糖水平和年龄对NASH影响显著。但在糖尿病患者中它们的作用相对降低；（3）DFL患者的肝酶活性一般没有明显变化。     

抵克力得、阿司匹林对糖尿病患者高纤维蛋白原血症影响的比较

目的观察抵克力得（T组）、阿司匹林（A组）对糖尿病（DM）高纤维蛋白原（FG）血症的治疗作用和副作用。方法选择无明显异常心电图和感染及脑梗死病史的DM高FG血症患者473例,随机分为两组,分别予抵克力得、阿司匹林治疗,以脑或心肌或皮肤梗死、出血倾向、白细胞减少事件为观察终点,治疗时间8～47个月,观察两组FG等炎性因子和临床终点事件的发生情况。结果T组的FG、WBC、hsC-RP明显降低,而A组则无明显变化;T组病人的心、脑、皮肤梗死和消化道、牙龈、皮肤出血倾向较A组病人明显减少;T组有6例发生白细胞减少症（A组0例）,但均未发生粒细胞缺乏和感染,且停药或（和）集落细胞刺激因子等升白细胞治疗后缓解。结论与阿司匹林相比,抵克力得治疗DM高FG血症更有效,并明显减少患者的梗死和出血倾向,但白细胞减少事件明显多于使用阿司匹林。在不宜使用阿司匹林（如过敏等）的病例可小心试用抵克力得。